p-Toluenesulfonic acid monohydrate → HCID 11714107, compound

HRID 1994563Notes

Reaction equation

HRID 1994563 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][CH:32]=[C:33]([C:35](O)([CH3:37])[CH3:36])[N:34]=3)[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][CH:32]=[C:33]([C:35]([CH3:37])=[CH2:36])[N:34]=3)[C@H:14]2[CH3:39])[CH:4]=[C:3]([C:2]([F:41])([F:40])[F:1])[CH:8]=1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 11621422HCID 11621422, compound

Product 1

HCID 11714107HCID 11714107, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[4-(1-hydroxy-1-methylethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (example 136) (9.5 mg, 0.015 mmol) in toluene (4 mL) was added p-toluenesulfonic acid monohydrate (20 mg, 0.105 mmol). The reaction was heated to 80° C. for 30 minutes and then cooled to room temperature, diluted with EtOAc (35 mL), and washed with saturated NaHCO3 and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(4-isopropenyl-1,3-thiazol-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.55 (40% EtOAc/hexanes). LCMS=595.1 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) δ 7.91 (s, 1H), 7.78-7.83 (m, 4H), 7.68 (d, J=8.5 Hz, 1H), 7.33 (s, 1H), 5.95 (d, J=0.9 Hz, 1H), 5.66 (d, J=8.0 Hz, 1H), 5.24 (m, 1H), 5.07 (d, J=16.4 Hz, 1H), 5.00 (d, J=16.3 Hz, 1H), 4.03 (m, 1H), 2.17 (s, 3H), 0.63 (d, J=6.4 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washwashed with saturated NaHCO3 and brine (15 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography on silica gel (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0fb43449b7d3485aab8f7bf33cdff99d
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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